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Current Molecular Pharmacology

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https://www.readbyqxmd.com/read/29766831/phagocytosis-and-motility-in-human-neutrophils-is-competent-but-compromised-by-pharmacological-inhibition-of-ezrin-phosphorylation
#1
Rhiannon E Roberts, Geetha L Elumalai, Maurice B Hallett
BACKGROUND AND OBJECTIVE: Ezrin links the cortical cytoskeleton to the plasma membrane and plays a role in regulating cell shape change. Recently NSC668394 has been shown to inhibit a key step for its activity, i.e. phosphorylation at threonine 567. In neutrophils, another key regulatory step is the Ca2+-mediated cleavage of ezrin by calpain. METHODS: In this paper we use NSC668394 as a pharmacological inhibitor to investigate the interplay between these two steps in regulating neutrophil shape change...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29766830/impact-of-sphingolipid-mediators-on-determination-of-cochlear-survival-in-ototoxicity
#2
Keiji Tabuchi, Akira Hara
BACKGROUND AND OBJECTIVE: Sphingolipid metabolites, including ceramide, sphingosine, and their phosphorylates (ceramide-1-phosphonate [C1P] and sphingosine-1-phosphate [S1P]), regulate diverse cellular processes including apoptosis, the cell cycle, and cellular differentiation. Recent studies have shown that these sphingolipid metabolites are generated in response to ototoxic agents and play important roles in determining the fate of cochlear hair cells in ototoxic injury. METHODS: This review summarizes the current knowledge on the roles of sphingolipid mediators in cochlear ototoxicity...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29741145/tandem-mass-spectrometric-cell-wall-proteome-profiling-of-a-candida-albicans-hwp2-mutant-strain
#3
Andy Awad, Pamela El Khoury, Brigitte Wex, Roy A Khalaf
BACKGROUND: Candida albicans is present as part of the normal gut flora and detected in the oral cavities and GI tracts of around fifty percent of adults. Benign colonization can turn pathogenic causing a variety of mild to severe infections. In a pathogen, the cell wall and cell surface proteins are major antigenic determinants and drug targets as they are the primary structures that contact the host. Cell surface proteins perform a variety of functions necessary for virulence such as adhesion, host degradation, resistance to oxidative stress, and drug resistance...
May 9, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29676239/transdermal-delivery-of-at1-receptor-antagonists-reduce-blood-pressure-and-reveals-a-vasodilatory-effect-in-kidney-blood-vessels
#4
Vasso Apostolopoulos, Michaila Michalatou, Maria-Eleni Androutsou, Markos Antonopoulos, George Agelis, Anthony Zulli, Tawar Qaradakhi, John Matsoukas
BACKGROUND: The Renin Angiotensin System (RAS) is pharmacologically targeted to reduce blood pressure, and patient compliance to oral medications is a clinical issue. The mechanisms of action of angiotensin receptor blockers (ARBs) in reducing blood pressure are not well understood, and is purported to be via a reduction of angiotensin II signaling. OBJECTIVE: We aimed to develop a transdermal delivery method for ARBs (losartan potassium and valsartan) and to determine if ARBs reveal a vasodilatory effect of the novel RAS peptide, alamandine...
April 19, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29485015/protein-tyrosine-phosphatase-as-potential-therapeutic-target-in-various-disorders
#5
Shivani Verma, Saurabh Sharma
Protein tyrosine phosphatase (PTP) class of enzymes functions in a unit with protein tyrosine kinases to regulate signaling pathways. Several members of the PTP family link to human disease predisposition such as PTP1B, SH2, DEP1, and inhibition of these enzymes may represent an effective palliative therapy. Protein tyrosine phosphatase inhibition has been intensively investigated as an important therapeutic target against metabolic syndrome and has been documented to improve hepatic insulin sensitivity, reduce liver triglycerides, cholesterol levels, and protects against endoplasmic reticulum (ER) stress...
February 26, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29468988/cox-2-in-radiotherapy-a-potential-target-for-radioprotection-and-radiosensitization
#6
Mohsen Cheki, Rasoul Yahyapour, Bagher Farhood, Abolhassan Rezaeyan, Dheyauldeen Shabeeb, Peyman Amini, Saeed Rezapoor, Masoud Najafi
BACKGROUND: Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology...
February 18, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29376497/l-sulforaphane-confers-protection-against-oxidative-stress-in-an-in-vitro-model-of-age-related-macular-degeneration
#7
Nabeela Khadija Dulull, Daniel Anthony Dias, Thilini Rasika Thrimawithana, Faith Ai Ai Kwa
BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal neovascularization in the retina are caused by the upregulation of vascular endothelium growth factor and reduced expression of Glutathione-S-transferase genes. Current treatments are only palliative. Compounds from cruciferous vegetables (e.g. L-Sulforaphane) have been found to restore normal gene expression levels in diseases including cancer via the activity of histone deacetylases and DNA methyltransferases, thus retarding disease progression...
January 25, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29357811/targeting-m3-muscarinic-receptors-for-colon-cancer-therapy
#8
Jessica Felton, Shien Hu, Jean-Pierre Raufman
BACKGROUND: Expression and activation of subtype-3 muscarinic receptors (M3R) plays an important role in the progression of colorectal neoplasia. METHODS: Herein, we describe the role of muscarinic receptors in colon cancer, focusing specifically on M3R, illustrate how M3R over-expression and activation of post-receptor signaling pathways potentiates tumor progression, and explore the efficacy and safety of a variety of therapeutic approaches that can target the molecules involved...
January 18, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29370747/editorial-corticotropin-releasing-factor-crf-and-its-receptors-from-structure-to-function-in-health-and-disease-part-ii
#9
EDITORIAL
George Liapakis
No abstract text is available yet for this article.
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29370746/preface
#10
Michael Kahn
No abstract text is available yet for this article.
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28260504/the-crf-family-of-neuropeptides-and-their-receptors-mediators-of-the-central-stress-response
#11
Nina Dedic, Alon Chen, Jan M Deussing
BACKGROUND: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2...
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28240194/brain-and-gut-crf-signaling-biological-actions-and-role-in-the-gastrointestinal-tract
#12
Yvette Tache, Muriel Larauche, Pu-Qing Yuan, Mulugeta Million
BACKGROUND: Corticotropin-releasing factor (CRF) pathways coordinate behavioral, endocrine, autonomic and visceral responses to stress. Convergent anatomical, molecular, pharmacological and functional experimental evidence supports a key role of brain CRF receptor (CRF-R) signaling in stress-related alterations of gastrointestinal functions. These include the inhibition of gastric acid secretion and gastric-small intestinal transit, stimulation of colonic enteric nervous system and secretorymotor function, increase intestinal permeability, and visceral hypersensitivity...
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28240193/crh-receptors-in-human-reproduction
#13
Antonis Makrigiannakis, Thomas Vrekoussis, Emmanuel Zoumakis, Iordanis Navrozoglou, Sophia N Kalantaridou
BACKGROUND: Corticotropin releasing hormone (CRH), the main peptide-mediator of stress, has been found in the female reproductive system. OBJECTIVE: Herein, the role of CRH receptors in the female reproductive system is presented. RESULTS: It is clear that CRH receptors are involved in the regulation of the hypothalamic-pituitaryovarian axis, while locally are associated with decidualization, embryonic implantation, early fetal development and triggering of parturition...
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28228090/cardioprotective-utility-of-urocortin-in-myocardial-ischemia-reperfusion-injury-where-do-we-stand
#14
Craig Basman, Pratik Agrawal, Richard Knight, Louis Saravolatz, Chad McRee, Carol Chen-Scarabelli, Jagat Narula, Tiziano Scarabelli
BACKGROUND: There has been a constant pursuit for development of newer therapies which can contribute to the relatively nascent field of cardioprotection in the setting of myocardial ischemiareperfusion injury. One novel cardioprotective agent among others, that has shown promising results in the limited number of research studies undertaken till now, is Urocortin. Urocortins are peptides belonging to the Corticotropin-Releasing Hormone family. RESULTS: Acting through a variety of downstream mechanisms, urocortin has been shown to alter cellular metabolism and modulate the mechanism of cell death occurring as a result of ischemia-reperfusion injury...
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28103784/the-multi-faceted-profile-of-corticotropin-releasing-factor-crf-family-of-neuropeptides-and-of-their-receptors-on-the-paracrine-local-regulation-of-the-inflammatory-response
#15
Eirini Dermitzaki, Maria Venihaki, Christos Tsatsanis, Achille Gravanis, Pavlina D Avgoustinaki, George Liapakis, Andrew N Margioris
BACKGROUND: The corticotropin releasing factor (CRF) family of neuropeptides, CRF and the Urocortins, and their receptors are present not only within the central nervous system but also in the periphery at various locations and at the sites of inflammation where they influence its progress in a complex local / paracrine manner. OBJECTIVE AND METHODS: This review summarizes current knowledge regarding the regulation of inflammatory process by CRF family of neuropeptides and receptors with a special sight into their role in inflammatory pain and in chronic low grade inflammation that occurs in obesity...
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/27784217/role-of-central-and-peripheral-crh-in-skin
#16
Olga Rassouli, George Liapakis, Maria Venihaki
BACKGROUND: Hypothalamic corticotrophin-releasing hormone (CRH) has a key role in coordinating and controlling complex responses to stress, both systemically, by stimulating the expression of the pituitary POMC gene, and thus, resulting in increased production of ACTH and adrenal glucocorticoid release, and locally since CRH has been identified in several peripheral tissues. CRH seems to exert its effects through interaction with two known so far receptors, CRF1R and CRF2R. The mRNA and protein of CRH family of peptides and their receptors are expressed at several peripheral tissues including rodent and human skin...
2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29119941/targeting-of-inflammation-for-radiation-protection-and-mitigation
#17
Rasoul Yahyapour, Peyman Amini, Saeed Rezapoor, Abolhasan Rezaeyan, Bagher Farhood, Mohsen Cheki, Hengameh Fallah, Masoud Najafi
Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect...
November 8, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29034844/microrna-cancer-and-diet-facts-and-new-exciting-perspectives
#18
Maria Letizia Motti, Stefania D'Angelo, Rosaria Meccariello
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs able to regulate gene expression at multiple levels. They are detected in tissues, blood, and other body fluids with high stability and have a recognized role in the maintaining of tissue homeostasis. Aberrant expression profile of miRNAs has been observed in several diseases, primarily cancer. As a consequence, the analysis of miRNA signature has recognized diagnostic and prognostic role in human diseases, and the development of miRNA-based therapies is currently under investigation...
October 13, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28969582/gamma-decanolactone-improves-biochemical-parameters-associated-with-pilocarpine-induced-seizures-in-male-mice
#19
Pricila Pflüger, Gabriela Gregory Regner, Vanessa R Coelho, Lucas Lima da Silva, Leopoldo Nascimento, Cassiana Macagnan Viau, Régis Adriel Zanette, Cleonice Hoffmann, Jaqueline Nascimento Picada, Jenifer Saffi, Patrícia Pereira
Gamma-decanolactone (GD) is a monoterpene effective against seizures induced by pentylenetetrazole. The mechanism of action of GD is likely to be via glutamate antagonism. GD also inhibits intracellular reactive oxygen species (ROS) generation and the lipopolysaccharide-induced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) in vitro. Considering the neuropharmacological profile of GD studied so far, we investigated the effect of intraperitoneal administration of GD 100 and 300 mg/kg on pilocarpine (PIL)-induced status epilepticus (SE) in mice...
October 2, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#20
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
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